1. Field of the Invention
The present invention relates to crosslinked elastomeric polymers suitable for use in the pharmaceutical industry.
2. Description of Information Disclosures
Rubber products, such as stoppers and linings for closures of containers used in the pharmaceutical industry, are in contact with pharmaceutical products which may extract some of the components of the rubber product and result in a contaminated pharmaceutical product which is discarded. The extraction problem is particularly exhibited when the rubber product is in contact with certain types of antibiotic formulations.
To overcome the problem of components being exuded from the rubber, higher purity rubber products containing less and fewer components which can be extracted from the rubber product by the pharmaceutical formulation are needed.
U.S. Pat. No. 4,721,756 discloses molded products, such as stoppers, eye drop tips and the like for use in the pharmaceutical industry. The molded rubber products are made from a composition comprising a halogenated butyl rubber and a curing system comprising specified amounts of zinc oxide and m-phenylene bismaleimide. The composition is formed in a premold and, thereafter, molded into shape by molding at a pressure of at least 500 psi at a temperature of up to 375.degree. F. for five minutes.
U.S. Pat. No. 4,803,250 discloses rubber compositions containing a sulfur vulcanization system comprising a sulfenamide type accelerator and a bismaleimide compound. The rubber component may be chloroprene.
U.S. Pat. No. 4,166,892 and U.S. Pat. No. 4,431,775 disclose a process for vulcanizing a rubber base comprising a halogen-containing amorphous polymer in the presence of a vulcanizing agent such as an organic peroxide and at least one member of the group selected from certain oxides of metals (e.g., zinc oxide); methacrylic esters; maleimides such as N,N'-m-phenylene bismaleimide; oximes and the like.
U.S. Pat. No. 2,996,473 discloses curing a halogenated copolymer of ethylene and an alpha olefin with a curing mixture which comprises a metal-containing substance, such as zinc oxide, and an organic polythiocarbonate.
U.S. Pat. No. 3,033,838 discloses that halogen-containing butyl type rubbers are vulcanizable with zinc oxide.
K. Ho et al, "Diels-Alder Reaction Curing of Chlorobutyl Rubber by Bis-Maleimides", Rubber Chemistry and Technology, vol. 62, pages 42 to 54, 1989 discloses that chlorinated butyl rubber can be crosslinked with N,N'-m-phenylene bis-maleimide via the diene groups on the chain generated by reaction with zinc oxide.
Vukov et al, "Crosslinking Efficiency of Some Halobutyl Curing Reactions", paper presented at the ACS Rubber Division Meeting, Denver, Colo., October 23-26, 1984, discloses the use of m-phenylene bis-maleimide and zinc oxide in crosslinking system for halobutyl rubber.
Crosslinked elastomers are known in which the molecular chains are crosslinked at the sites of the carbon to carbon double bond, of the uncrosslinked initial polymer, as well as at the site of other functional groups present in the uncrosslinked polymer, such as, for example at the site of chemically-bound halogen.
Partially crosslinked polymers are known such as those disclosed in U.S. Pat. Nos. 2,781,334 and 2,729,626 in which the polymers are prepared by copolymerizing an isoolefin with a conjugated diolefin and a divinyl benzene. Such polymers require the use of divinyl benzene in its preparation as well as the use of the isoolefin and the conjugated diolefin. A brochure of Polysar Corporation discloses Polysar.RTM. Butyl Terpolymers such as XL 10,000 (previously XL-20), including Polysar.RTM. Butyl Terpolymer XL 40302 which is described as a halogenated type (printed in Canada, 1988).
Halogenated butyl rubber having a low level of halogen e.g., chlorine content of about 0.5 mole percent (about 0.3 wt. %) and a low level of non-halogenated isoprene unsaturation are disclosed in a paper entitled "Chlorobutyl Designed for Curing Members" authored by J. V. Fusco, I. J. Gardner, P. Hous and D. S. Tracey presented at a meeting of the Rubber Division, American Chemical Society, Mexico City, Mexico, May 9-12, 1989, paper No. 57, and in European patent application number 89310227.7 filed Oct. 5, 1989.
Numerous patents disclose halogenated butyl rubber containing various amounts of chemically bound halogen, for example, U.S. Pat. No. 2,631,984 discloses brominated butyl rubber containing at least 0.5 weight percent bromine; U.S. Pat. No. 2,732,354 discloses chlorinated butyl rubber containing from 0.4 to 2.3 weight percent chlorine; U.S. Pat. No. 3,099,644 discloses a process for the continuous halogenation of butyl rubber to produce a halogenated rubber containing 1.13 weight percent chlorine. U.S. Pat. No. 2,732,354 discloses chlorinated butyl rubber containing from about 0.4 to 2.3 weight percent of chlorine. U.S. Pat. No. 2,944,578 describes compositions comprising chlorinated butyl rubber in which the butyl rubber has been substitutively chlorinated to contain at least 0.5 weight percent chlorine; FIG. II of this patent appears to include a data point at about 0.6 wt. percent chlorine. U.S. Pat. No. 3,099,644 discloses a process for the continuous halogenation of butyl rubber to produce a halogenated rubber containing 1.13 weight percent chlorine. U.S. Pat. No. 2,943,664 discloses adhesive compositions for tire cords comprising chlorinated butyl rubber containing at least 0.5 percent by weight of combined chlorine. U.S. Pat. No. 2,964,489 discloses a process for the production of tubeless tires and curing bladders containing 0.5 weight percent chlorine. The chlorine content of known chlorinated butyl rubber is typically defined by a formula, as shown, for example, in U.S. Pat. No. 2,964,489 (column 2, lines 50-60) and expressed as being "at least 0.5 wt. percent (preferably at least about 1.0 wt. percent) combined chlorine." In a restatement of the chlorine concentration, it is stated that there should be "at least 0.2 and preferably at least about 0.5 weight percent of combined chlorine in the polymer." (id, lines 60-62). U.S. Pat. No. 4,130,534 discloses elastoplastic compositions comprising a blend of thermoplastic crystalline polyolefin resin and a butyl rubber, crosslinked to the extent that it is at least 90 percent gelled. It defines butyl rubber (at column 5, lines 17-34) to include "copolymers of isobutylene and isoprene containing 0.5 to 10, more preferably 1 to 4 percent by weight isoprene and said copolymers halogenated with from 0.1 to about 10, preferably 0.5 to 3.0 weight percent chlorine or bromine which chlorinated copolymer is commonly called chlorinated butyl rubber".
U.S. Pat. No. 3,758,643 and U.S. Pat. No. 3,862,106 (W. K. Fischer) disclose a partially crosslinked EPDM polymer having a gel content of at least 30 percent but less than 90 percent by weight as measured by immersion in cyclohexane for 48 hours at 73.degree. F.
It is known to perform melt phase reaction of polymers in continuous flow devices, such as extruder-reactors. See, for example, U.S. Pat. Nos. 4,513,116; 4,548,995; 4,554,326, and 4,563,506, the teachings of which are hereby incorporated by reference.
U.S. Pat. No. 4,594,390 discloses the use of an extruder to prepare thermoplastic compositions comprising a blend of plastic and cured rubber.
It has now been found that a crosslinked, unsaturated copolymer prepared by crosslinking a specified halogen-containing copolymer utilizing a specified curing mixture has a decreased tendency to exude into pharmaceutical formulations.